Fol. Biol. 2012, 58, 81-86

https://doi.org/10.14712/fb2012058020081

PAR2 Knock-Out C57Bl6 Mice as a Model for Evaluating Metastases of Cancer Cells: Pilot in Vivo Study of the Metastatic Potential of B16 Melanoma in Knock-Out (PAR2-/-) Animals

Radoslav Matěj1,2, M. Zadinová3, P. Poučková3, J. Kukal4, T. Olejár1,3

1Department of Pathology and Molecular Medicine, Thomayer Teaching Hospital, Prague, Czech Republic
2Department of Pathology, Third Faculty of Medicine, Charles University in Prague, Czech Republic
3Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University in Prague, Czech Republic
4Department of Software Engineering in Economy, Faculty of Nuclear Science and Physical Engineering, Czech Technical University, Prague, Czech Republic

Received August 2011
Accepted November 2011

Proteinase-activated receptor 2 (PAR-2) is a ubiquitous surface molecule. It belongs to the family of G protein-coupled receptors activated by sitespecific proteolysis by trypsin. Altered function of PAR-2 has been described in different malignant tumours, both in vivo and in vitro. In the present study, we investigated differences of metastatic spread of B16 melanoma in knock-out animals compared with C57Bl6 mice. Knock-out mice B6.Cg-F2rl1tm1Mslb/J (PAR2-/-) and C57Bl6 controls were subcutaneously inoculated with the B16 melanoma tissue cell line. Fourteen days after inoculation, all primary tumours were removed and histopathologically analysed. After one month, animals in both group started to die. Autopsy showed metastatic spread of the melanoma to various organs in both groups. Our experiment confirmed growth and metastatic spread in both groups of mice. Excised tumours differed in volume and weight; average weight (0.62 g in PAR2-/and 0.4 g in control animals). Metastatic spread was observed in both groups and reached 80 % in PAR2-/and 50 % in control animals. While in control mice only lung metastases were observed, local tumour recurrence, renal and lung metastases were observed in PAR2-/mice. The absence of functional PAR-2 could be an important factor influencing the growth and spread of melanoma in vivo, probably associated with tumour cell migration, invasiveness and metastasis formation.

Funding

This study was partly supported by IGA MZ NS/10423-3 and Grant No. 309/09/P204 of the Grant Agency of the Czech Republic.

References

21 live references